This invention relates to planar microfluidic devices and their manufacture. Microfluidic devices have a wide range of existing and potential uses in various arts. Of particular importance are microfluidic devices for use as electrochemical microsensors for chemical detection and measurement, especially in biochemical applications such as in medicine. In order to succeed in the point of care market, the biosensor systems must meet their application needs. Planar electrochemical sensors with microelectronic production techniques are known as an elegant approach to meet these requirements. Due to the batch processing and high precision of microelectronic techniques, the miniaturized planar sensors have major advantages including small dimension, low cost per sensor, high reproducibility and the possibility of smart sensor realizations. In the past few years, a number of mnicro-fabricated sensors have been designed and developed by microelectronic techniques. These sensors are usually made on silicon and include integrated electronic elements. The are usable for detecting various ions as well as gases. However, in these cases, silicon is only a substrate and does not play any role in the sensing mechanism itself. There also exist some problems concerning the final package of the sensors because a chemical sensor on an insulating substrate is almost always easier to package than on a piece of silicon with conductive edges in need of insulation. Moreover, many chemical sensor materials are incompatible with IC processing; therefore the very point of using silicon is forfeit for many chemical sensors. Lately, flexible polyimide film (Kapton) has been used as a substrate in micro-fabricated planar sensor arrays. Photolithography and sputtering technologies are used in the fabrication of the sensor arrays. These sensor arrays have shown good analytical properties in-vivo measurements and solved the problems with respect to membrane optimization, adhesion of membrane to its substrate, etc., but the sputtering process causes the fabrication of sensors to be expensive and time consuming.
As for the configuration of these sensors, the sensor sites and their electrical contacts are on the same side of the substrate. This makes the fabrication of multi-purpose sensor arrays more complicated with a lower production yield. In order to make disposable micro-electrochemical sensors, we believe an elegant approach can be realized by merging IC and screen printing process from silicon wafers to large sheets of dry photoresist films. A modular approach is preferred since there are no electronics on the chip and one only wants to fabricate an array of chemical sensors. This modular approach enables the independent development of different sensors, obviates many compatibility issues, and increases the manufacturing yield dramatically.
At the same time, microfluidic devices are increasingly used in applications for drug discovery and diagnostic area. By using the precise control of flow in microchannels to larger fluidic components, the mixing and the partition of the fluidics with very small samples can be realized. A wide variety of fluidic processes can be carried out with different flow speeds in a combination of pressure-dependent and pressure independent valves. The current method of manufacturing for microfluidics is using a conventional LIGA process for anisotropically etching the microchannels in the silicon wafer with high aspect ratio. Silicon bonding technology is also needed to make a buried channel. However, since the LIGA process needs X-ray sources, which is very expensive, it is difficult to make a cheap disposable microfluidic platform with the conventional approach.
This invention relates to a new design and fabrication process for microfluidic devices including miniaturized electrochemical sensors. The invention provides microfluidic structures that may be processed and adapted for a wide variety of end uses. In this new design, identical devices, such as miniaturized electrochemical sensors, may be fabricated on sheets of a non-silicon material substrate by a batch, modular-manufacturing methodology. The modular structures each may have one or more microchambers. The microchambers of these structures may be processed while in sheet form appropriately for the end use contemplated. Microchambers of modular structures intended for use as sensors or reference electrodes may be charged with electrolytic media or analytes appropriate to the desired sensor or electrode end use. The individual devices may then separated from the sheet and then integrated into appropriate combinations or systems, such as multiple analyte sensor arrays, using pick and place technology. By fabricating identical miniaturized devices on a single large sheet of substrate the yield substantially increases over conventional substrates.
In this invention microfluidic devices are fabricated by a low cost methodology utilizing negative photoresists as a matrix for these devices. A laminate is formed comprising a negative photoresist matrix layer on a non-silicon support layer. The negative matrix photoresist layer is exposed to radiation through a mask that defines the cavities or wells for the desired microfluidic chambers to thereby fix the photoresist layer at exposed areas and leave this layer unfixed at the masked areas. The matrix photoresist is then developed to remove the photoresist layer at the unfixed areas to thereby form the cavities for the microfluidic devices. A membrane is applied at the surface of the matrix photoresist layer to enclose the wells and form the desired microfluidic chambers. The membrane is provided with one or more small holes or pores at the chambers or channels to provide fluid communication with the chambers to and from the outside, as appropriate to the end use of the devices.
In one feature of the invention, a preformed or xe2x80x9cdryxe2x80x9d negative photoresist layer is applied to the surface of the matrix photoresist layer as a membrane to cover the cavities. Following its application the covering photoresist is irradiated to fix it to a durable and permanent state. Where applicable, the covering photoresist layer may be exposed to radiation through a mask that defines fluid communication holes, at chamber locations, appropriate to the end use of the microfluidic devices. The second photoresist layer is then developed to form the fluid communication holes through the second photoresist to the chambers. However, without regard to its normal intended function as a photoresist to form a layer with cavities or other desired discontinuities, it has been discovered that application of a dry photoresist to cover the cavities in the matrix layer, as described, is uniquely advantageous. The dry photoresist in this application has been found to bond strongly to the matrix layer without migrating into and clogging the wells, channels and other cavities in the matrix layers for the microfluidic device, as experienced with other types of covering materials.
In another feature of this invention important to microfluidic devices for use as sensors a pre-formed negative photoresist is employed as the support layer for the matrix photoresist layer. In this embodiment, a photo-opaque conductive material, such as silver, is applied to the surface a self-supporting negative photoresist film in discrete spots to form an electrode at each location at which a sensor is to be formed. A negative photoresist matrix layer is applied to the support layer at the side bearing the electrodes to form a laminate in which the electrodes are at the interface of the matrix and support layers. The laminate is exposed to radiation at the matrix layer side while a mask is aligned with each electrode of a size to define the desired cavity for a microfluidic chamber over the electrode but having a span smaller than that of the electrode. The matrix photoresist is thereby fixed across the unmasked surface and remains unfixed at the area below the mask and the substrate photoresist is thereby fixed across its span except for the area below the electrode. Both the matrix photoresist and substrate photoresist are then developed to remove the photoresist layer at the unfixed areas. Wells are thus formed in both the matrix layer and in the substrate layer that extend to the electrodes at the interface therebetween. A membrane may then be applied at the surface of the matrix photoresist layer to enclose the cavities and form the desired microfluidic chambers. The membrane may be provided with one or more small holes or pores at the chambers or channels to provide fluid communication with the chambers to and from the outside, as appropriate to the end use of the devices. The wells in the substrate layer may be employed for electrical communication with the electrodes of the sensors. For this purpose each well may receive an electrical contact pin for contacting the electrode.
In yet another feature of the invention sensors are integrated into arrays in biomodules having fluidic communication channels to the individual sensors. An array of sensors is arranged on a biomodule substrate and a cover arranged across the substrate over sensors which is provided with fluid communication ports to the outside and internal channels above the sensors to provide fluid communication each sensor and the external ports. A preformed negative photoresist may be applied to the biomodule substrate for the cover and then irradiated to fix the photoresist. Internal pillars or walls, preferably also by photoresist application, may be applied to the biomodule substrate, prior to application to the cover, to serve as a bridge to support the cover above the sensors, thereby to form a common communication chamber over the sensors.